Faculty Bibliography

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is frequently responsible for chronic hyponatremia in the elderly due to age-related disruption of the inhibitory component of brain osmoregulatory mechanisms. Recent research has indicated that chronic hyponatremia is associated with gait disturbances, increased falls, and bone fragility in humans, and we have found that chronic hyponatremia causes increased bone resorption and reduced bone mineral density in young rats. In this study, we used a model of SIADH to study multi-organ consequences of chronic hyponatremia in aged rats. Sustained hyponatremia for 18 weeks caused progressive reduction of bone mineral density by DXA and decreased bone ash calcium, phosphate and sodium contents at the tibia and lumbar vertebrae. Administration of 10-fold higher vitamin D during the last 8 weeks of the study compensated for the reduction in bone formation and halted bone loss. Hyponatremic rats developed hypogonadism, as indicated by slightly lower serum testosterone and higher serum FSH and LH concentrations, markedly decreased testicular weight, and abnormal testicular histology. Aged hyponatremic rats also manifested decreased body fat, skeletal muscle sarcopenia by densitometry, and cardiomyopathy manifested as increased heart weight and perivascular and interstitial fibrosis by histology. These findings are consistent with recent results in cultured osteoclastic cells, indicating that low extracellular sodium concentrations increased oxidative stress, thereby potentially exacerbating multiple manifestations of senescence. Future prospective studies in patients with SIADH may indicate whether these multi-organ age-related comorbidities may potentially contribute to the observed increased incidence of fractures and mortality in this population.

This study examined the comorbidity of anxiety disorders and its predictors in a large, clinically referred sample of children and adolescents. Participants were 608 youth aged 4-18 years presenting at a large anxiety clinic for assessment and treatment of anxiety or mood related problems. The diagnoses were determined using the Anxiety Disorder Interview Schedule, Child/Parent versions. Sixty three percent of the participants had an additional diagnosis of an anxiety or depressive disorder. Comorbidity patterns differed based on the principal diagnostic category. Older children and females with anxiety were more likely to have a comorbid anxiety disorder. The presence of a medical condition increased the odds of having a comorbid anxiety disorder as well. This is the largest clinical sample of children and adolescents in which comorbidity of emotional disorders has been examined. Understanding the common patterns of comorbidity has important implications for future classification and treatment planning of childhood anxiety disorders.

It is notoriously difficult to name odours. Without the benefit of non-olfactory information, even common household smells elude our ability to name them. The neuroscientific basis for this olfactory language 'deficit' is poorly understood, and even basic models to explain how odour inputs gain access to transmodal representations required for naming have not been put forward. This study used patients with primary progressive aphasia, a clinical dementia syndrome characterized by primary deficits in language, to investigate the interactions between olfactory inputs and lexical access by assessing behavioural performance of olfactory knowledge and its relationship to brain atrophy. We specifically hypothesized that the temporal pole would play a key role in linking odour object representations to transmodal networks, given its anatomical proximity to olfactory and visual object processing areas. Behaviourally, patients with primary progressive aphasia with non-semantic subtypes were severely impaired on an odour naming task, in comparison with an age-matched control group. However, with the availability of picture cues or word cues, odour matching performance approached control levels, demonstrating an inability to retrieve but not to recognize the name and nature of the odorant. The magnitude of cortical thinning in the temporal pole was found to correlate with reductions in odour familiarity and odour matching to visual cues, whereas the inferior frontal gyrus correlated with both odour naming and matching. Volumetric changes in the mediodorsal thalamus correlated with the proportion of categorical mismatch errors, indicating a possible role of this region in error-signal monitoring to optimize recognition of associations linked to the odour. A complementary analysis of patients with the semantic subtype of primary progressive aphasia, which is associated with marked temporopolar atrophy, revealed much more pronounced impairments of odour naming and matching. In identifying the critical role of the temporal pole and inferior frontal gyrus in transmodal linking and verbalization of olfactory objects, our findings provide a new neurobiological foundation for understanding why even common odours are hard to name.

Attention Bias Modification Treatment (ABMT), an emerging treatment for anxiety disorders, is thought to modify underlying, stable patterns of attention. Therefore, ABMT research should take into account the impact of attention bias stability on attention training response, especially in pediatric populations. ABMT research typically relies on the dot-probe task, where individuals detect a probe following an emotional-neutral stimulus pair. The current research presents two dot-probe experiments relevant to ABMT and attention-bias stability. In Experiment 1, anxious youth receiving 8-weeks of cognitive-behavioral therapy (CBT) were randomly assigned to ABMT that trains attention towards happy faces (n=18) or placebo (n=18). Two additional comparison groups, anxious youth receiving only CBT (n=17) and healthy comparison youth (n=16), were studied. Active attention training towards happy faces did not augment clinician-rated response to CBT; however, individuals receiving training exhibited reductions on self-report measures of anxiety earlier than individuals receiving CBT only. In Experiment 2, healthy youth (n=12) completed a dot-probe task twice while undergoing functional magnetic resonance imaging. Intra-class correlation demonstrated stability of neural activation in response to attention bias in the ventrolateral prefrontal cortex and amygdala. Together, these two studies investigate the ways in which attention-bias stability may impact future work on ABMT.

PURPOSE: Remelted highly crosslinked polyethylenes (HXLPEs) were introduced in total knee replacement (TKR) starting in 2001 to reduce wear and particle-induced lysis. The purpose of this study was to investigate the damage mechanisms and oxidative stability of remelted HXLPEs used in TKR. METHODS: A total of 186 posteriorly stabilised tibial components were retrieved at consecutive revision operations. Sixty nine components were identified as remelted HXLPE. The conventional inserts were implanted for 3.4 +/- 2.7 years, while the remelted components were implanted 1.4 +/- 1.2 years. Oxidation was assessed using Fourier transform infrared spectroscopy. RESULTS: Remelted HXLPE inserts exhibited lower oxidation indices compared to conventional inserts. We were able to detect slight regional differences within the HXLPE cohort, specifically at the bearing surface. CONCLUSION: Remelted HXLPE was effective at reducing oxidation in comparison to gamma inert sterilised controls. Additional long-term HXLPE retrievals are necessary to ascertain the long term in vivo stability of these materials in TKR.

OBJECTIVE: Attention bias modification training (ABMT) is a promising treatment. Nevertheless, few studies examine its effectiveness in anxious children. This study examined the efficacy of such an ABMT protocol in pediatric anxiety. METHOD: 37 anxious children were randomly assigned to one of two ABMT conditions. In the attention-towards-positive (ATP) condition, children searched 3x3 matrices for a happy face amongst angry faces. In the attention-training-control (ATC) condition, they searched for a bird amongst flowers. Children completed 160 trials in each of four training sessions per week for three weeks at home (1920 total trials). Clinical and attention bias measures were assessed before and after ABMT. RESULTS: Children randomized to ATP showed greater post-training attention bias towards happy faces than children randomized to ATC. ATP also produced significantly greater reductions in clinician-rated diagnostic severity and number of diagnoses, compared to ATC. In the ATP group, 50% of children who completed training did not meet criteria for their principal diagnosis, compared to 8% in the ATC group. CONCLUSION: Training anxious children to focus attention on positive features of their environment may be a promising treatment.

IMPORTANCE: Combat places soldiers at risk for posttraumatic stress disorder (PTSD). The excessive rates of PTSD and other adjustment disorders in soldiers returning home make it imperative to identify risk and resilience factors that could be targeted by novel therapeutic treatments. OBJECTIVE: To investigate the interplay among attention to threat, combat exposure, and other risk factors for PTSD symptoms in soldiers deployed to combat. DESIGN AND SETTING: Longitudinal prospective study of Israeli Defense Force infantry soldiers carried out in 2008 through 2010. Repeated measurements during a 1-year period included baseline and predeployment data collected in training camps and deployment data collected in the combat theater. PARTICIPANTS: Infantry soldiers (1085 men; mean age, 18.8 years). MAIN OUTCOME MEASURES: Postcombat PTSD symptoms. RESULTS Soldiers developed threat vigilance during combat deployment, particularly when they were exposed to high-intensity combat, as indicated by faster response times to targets appearing at the location of threat relative to neutral stimuli (P < .001). Threat-related attention bias also interacted with combat exposure to predict risk for PTSD (P < .05). Bias toward threat at recruitment (P < .001) and bias away from threat just before deployment (P < .05) predicted postcombat PTSD symptoms. Moreover, these threat-related attention associations with PTSD were moderated by genetic and environmental factors, including serotonin transporter (5-HTTLPR) genotype. CONCLUSIONS AND RELEVANCE: Combat exposure interacts with threat-related attention to place soldiers at risk for PTSD, and interactions with other risk factors account for considerable variance in PTSD vulnerability. Understanding these associations informs research on novel attention bias modification techniques and prevention of PTSD.

BACKGROUND: Overweight and obese adolescents commonly underestimate their weight status, considering themselves to be at a healthy weight or underweight. These adolescents are more likely to be male, older, and Latino, black, or Native American. Associations with acculturation have not been previously assessed. The goal of this study was to identify the prevalence of underestimation of weight status in Californian adolescents and to identify factors associated with this underestimation, in particular examining relationships with race/ethnicity and acculturation. METHODS: Secondary data analysis of the 2005 Adolescent California Health Interview Survey. RESULTS: A total of 36.6% of overweight and obese Californian adolescents underestimated their weight status. Adolescents not born in the United States had increased odds of underestimating their weight status compared to those born in the United States [adjusted odds ratio (aOR)=1.94, 95% confidence interval (CI) 1.08, 3.49; p=0.03]. No significant associations with race/ethnicity were found. An age-sex interaction was observed with older adolescent males having increased odds compared to younger females. CONCLUSIONS: Identification of individuals at increased odds of underestimating their weight status may be important in developing and targeting appropriate counseling and interventions to ameliorate long-term health risks of excess weight.

Limited socioeconomic family and neighborhood resources are known to influence multiple aspects of school readiness skills. Early parent involvement in education is hypothesized to attenuate risk for academic underachievement related to socioeconomic disadvantage. The current study used multilevel modeling to test whether parent involvement moderates the effects of family and neighborhood level socioeconomic resources on school readiness among a sample of 171 urban 4-year-olds. Parent involvement moderated the effect of family and neighborhood socioeconomic resources on the social-emotional-behavioral components of school readiness. Increased parent involvement in education was related to lower rates of behavior problems among children of single parents and among children from neighborhoods with higher levels of childcare burden. In contrast, parent involvement did not moderate the relation between socioeconomic risk and cognitive-academic components of school readiness skills